Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status

Autor: Yuwei Wang, Gwen M. H. E. Dackus, Efraim H. Rosenberg, Sten Cornelissen, Leonora W. de Boo, Annegien Broeks, Wim Brugman, Terry W. S. Chan, Paul J. van Diest, Michael Hauptmann, Natalie D. ter Hoeve, Olga I. Isaeva, Vincent M. T. de Jong, Katarzyna Jóźwiak, Roelof J. C. Kluin, Marleen Kok, Esther Koop, Petra M. Nederlof, Mark Opdam, Philip C. Schouten, Sabine Siesling, Charlaine van Steenis, Adri C. Voogd, Willem Vreuls, Roberto F. Salgado, Sabine C. Linn, Marjanka K. Schmidt
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Medicine, Vol 22, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 1741-7015
DOI: 10.1186/s12916-023-03233-7
Popis: Abstract Background Due to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account. Methods We included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients’ outcomes were compared using Cox regression and competing risk models. Results Among the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18–3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78–0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and ≥ 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9–100%). Conversely, among the 61 patients with gBRCA1m and
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